Alain H. Litwin

Recommendations for the management of hepatitis C virus infection among people who inject drugs

In high income countries, the majority of new and existing hepatitis C virus (HCV) infections occur among people who inject drugs (PWID). In many low and middle income countries large HCV epidemics have also emerged among PWID populations. The burden of HCV-related liver disease among PWID is increasing, but treatment uptake remains extremely low. There are a number of barriers to care which should be considered and systematically addressed, but should not exclude PWID from HCV treatment. The rapid development of interferon-free direct-acting antiviral (DAA) therapy for HCV infection has brought considerable optimism to the HCV sector, with the realistic hope that therapeutic intervention will soon provide near optimal efficacy with well-tolerated, short duration, all oral regimens. Further, it has been clearly demonstrated that HCV treatment is safe and effective across a broad range of multidisciplinary healthcare settings. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment and treatment in this group are urgently needed. These recommendations demonstrate that treatment among PWID is feasible and provide a framework for HCV assessment and care. Further research is needed to evaluate strategies to enhance testing, linkage to care, treatment, adherence, viral cure, and prevent HCV reinfection among PWID, particularly as new interferon-free DAA treatments for HCV infection become available.

Elbasvir-grazoprevir to treat hepatitis C virus infection in persons receiving opioid agonist therapy a randomized trial

Background Hepatitis C virus (HCV) infection is common in persons who inject drugs (PWID). Objective To evaluate elbasvir-grazoprevir in treating HCV infection in PWID. Design Randomized, placebo-controlled, double-blind trial. (ClinicalTrials.gov: NCT02105688). Setting Australia, Canada, France, Germany, Israel, the Netherlands, New Zealand, Norway, Spain, Taiwan, the United Kingdom, and the United States. Patients 301 treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection who were at least 80% adherent to visits for opioid agonist therapy (OAT). Intervention The immediate-treatment group (ITG) received elbasvir-grazoprevir for 12 weeks; the deferred-treatment group (DTG) received placebo for 12 weeks, no treatment for 4 weeks, then open-label elbasvir-grazoprevir for 12 weeks. Measurements The primary outcome was sustained virologic response at 12 weeks (SVR12), evaluated separately in the ITG and DTG. Other outcomes included SVR24, viral recurrence or reinfection, and adverse events. Results The SVR12 was 91.5% (95% CI, 86.8% to 95.0%) in the ITG and 89.5% (95% CI, 81.5% to 94.8%) in the active phase of the DTG. Drug use at baseline and during treatment did not affect SVR12 or adherence to HCV therapy. Among 18 patients with posttreatment viral recurrence through 24-week follow-up, 6 had probable reinfection. If the probable reinfections were assumed to be responses, SVR12 was 94.0% (CI, 89.8% to 96.9%) in the ITG. One patient in the ITG (1 of 201) and 1 in the placebo-phase DTG (1 of 100) discontinued treatment because of an adverse event. Limitation These findings may not be generalizable to PWID who are not receiving OAT, nor do they apply to persons with genotype 3 infection, a common strain in PWID. Conclusion Patients with HCV infection who were receiving OAT and treated with elbasvir-grazoprevir had high rates of SVR12, regardless of ongoing drug use. These results support the removal of drug use as a barrier to interferon-free HCV treatment for patients receiving OAT. Primary Funding Source Merck & Co.

Models of Care for the Management of Hepatitis C Virus Among People Who Inject Drugs: One Size Does Not Fit All

One of the major obstacles to hepatitis C virus (HCV) care in people who inject drugs (PWID) is the lack of treatment settings that are suitably adapted for the needs of this vulnerable population. Nevertheless, HCV treatment has been delivered successfully to PWID through various multidisciplinary models such as community-based clinics, substance abuse treatment clinics, and specialized hospital-based clinics. Models may be integrated in primary care--all under one roof in either addiction care units or general practitioner-based models--or can occur in secondary or tertiary care settings. Additional innovative models include directly observed therapy and peer-based models. A high level of acceptance of the individual life circumstances of PWID rather than rigid exclusion criteria will determine the level of success of any model of HCV management. The impact of highly potent and well-tolerated interferon-free HCV treatment regimens will remain negligible as long as access to therapy cannot be expanded to the most affected risk groups.

Successful treatment of chronic hepatitis C with pegylated interferon in combination with ribavirin in a methadone maintenance treatment program

Injection drug users constitute 60% of the more than 4 million people in the United States with hepatitis C virus (HCV), including many methadone maintenance patients. Few data exist describing clinical outcomes for patients receiving HCV treatment on-site in methadone maintenance settings. In this retrospective study, we describe clinical outcomes for 73 patients receiving HCV treatment on-site in a methadone maintenance treatment program. Fifty-five percent of patients achieved end-of-treatment response, and 45% achieved sustained viral response. These treatment response rates are nearly equivalent to previously published HCV treatment response rates, despite high prevalences of ongoing drug use (49%), psychiatric comorbidity (67%), and HIV coinfection (32%). These data show that on-site HCV treatment with pegylated interferon and ribavirin is effective in methadone-maintained patients, many of whom are active drug users, psychiatrically ill, or HIV coinfected, and that methadone maintenance treatment programs represent an opportunity to safely treat chronic hepatitis C.

Directly observed antiretroviral therapy improves adherence and viral load in drug users attending methadone maintenance clinics: A randomized controlled trial

OBJECTIVE To determine if directly observed antiretroviral therapy (DOT) is more efficacious than self-administered therapy for improving adherence and reducing HIV viral load (VL) among methadone-maintained opioid users. DESIGN Two-group randomized trial. SETTING Twelve methadone maintenance clinics with on-site HIV care in the Bronx, New York. PARTICIPANTS HIV-infected adults prescribed combination antiretroviral therapy. MAIN OUTCOMES MEASURES Between group differences at four assessment points from baseline to week 24 in: (1) antiretroviral adherence measured by pill count, (2) VL, and (3) proportion with undetectable VL (< 75 copies/ml). RESULTS Between June 2004 and August 2007, we enrolled 77 participants. Adherence in the DOT group was higher than in the control group at all post-baseline assessment points; by week 24 mean DOT adherence was 86% compared to 56% in the control group (p < 0.0001). Group differences in mean adherence remained significant after stratifying by baseline VL (detectable versus undetectable). In addition, during the 24-week intervention, the proportion of DOT participants with undetectable VL increased from 51% to 71%. CONCLUSIONS Among HIV-infected opioid users, antiretroviral DOT administered in methadone clinics was efficacious for improving adherence and decreasing VL, and these improvements were maintained over a 24-week period. DOT should be more widely available to methadone patients.

Integrating Services for Injection Drug Users Infected with Hepatitis C Virus with Methadone Maintenance Treatment: Challenges and Opportunities

Despite the high prevalence of hepatitis C virus (HCV) infection among drug users enrolled in methadone maintenance treatment programs, few drug users are being treated with combination therapy. The most significant barrier to treatment is lack of access to comprehensive HCV-related care. We describe a pilot program to integrate care for HCV infection with substance abuse treatment in a setting of maintenance treatment with methadone. This on-site, multidisciplinary model of care includes comprehensive screening and treatment for HCV infection, assessment of eligibility, counseling with regard to substance abuse, psychiatric services, HCV support groups, directly observed therapy, and enhanced linkages to a tertiary care system for diagnostic procedures. Our approach has led to high levels of adherence, with liver biopsy and substantial rates of initiation of antiviral therapy. Two cases illustrate the successful application of this model to patients with HCV infection complicated by active substance abuse and psychiatric comorbidity.

The new paradigm of hepatitis C therapy: integration of oral therapies into best practices

Emerging data indicate that all‐oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon‐based therapies, all‐oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk‐based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one‐time testing for all persons born during 1945–1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk‐based and birth‐cohort‐based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels.

Primary care-based interventions are associated with increases in hepatitis C virus testing for patients at risk

BACKGROUND An estimated 3.2 million persons are chronically infected with the hepatitis C virus (HCV) in the U.S. Effective treatment is available, but approximately 50% of patients are not aware that they are infected. Optimal testing strategies have not been described. METHODS The Hepatitis C Assessment and Testing Project (HepCAT) was a serial cross-sectional evaluation of two community-based interventions designed to increase HCV testing in urban primary care clinics in comparison with a baseline period. The first intervention (risk-based screener) prompted physicians to order HCV tests based on the presence of HCV-related risks. The second intervention (birth cohort) prompted physicians to order HCV tests on all patients born within a high-prevalence birth cohort (1945-1964). The study was conducted at three primary care clinics in the Bronx, New York. RESULTS Both interventions were associated with an increased proportion of patients tested for HCV from 6.0% at baseline to 13.1% during the risk-based screener period (P<0.001) and 9.9% during the birth cohort period (P<0.001). CONCLUSIONS Two simple clinical reminder interventions were associated with significantly increased HCV testing rates. Our findings suggest that HCV screening programs, using either a risk-based or birth cohort strategy, should be adopted in primary care settings so that HCV-infected patients may benefit from antiviral treatment.

Hepatitis C testing practices and prevalence in a high-risk urban ambulatory care setting.

Summary.  Approximately 3.2 million persons are chronically infected with the hepatitis C virus (HCV) in the U.S.; most are not aware of their infection. Our objectives were to examine HCV testing practices to determine which patient characteristics are associated with HCV testing and positivity, and to estimate the prevalence of HCV infection in a high‐risk urban population. The study subjects were all patients included in the baseline phase of the Hepatitis C Assessment and Testing Project (HepCAT), a serial cross‐sectional study of HCV screening strategies. We examined all patients with a clinic visit to Montefiore Medical Center from 1/1/08 to 2/29/08. Demographic information, laboratory data and ICD‐9 diagnostic codes from 3/1/97–2/29/08 were extracted from the electronic medical record. Risk factors for HCV were defined based on birth date, ICD‐9 codes and laboratory data. The prevalence of HCV infection was estimated assuming that untested subjects would test positive at the same rate as tested subjects, based on risk‐factors. Of 9579 subjects examined, 3803 (39.7%) had been tested for HCV and 438 (11.5%) were positive. The overall prevalence of HCV infection was estimated to be 7.7%. Risk factors associated with being tested and anti‐HCV positivity included: born in the high‐prevalence birth‐cohort (1945–64), substance abuse, HIV infection, alcohol abuse, diagnosis of cirrhosis, end‐stage renal disease, and alanine transaminase elevation. In a high‐risk urban population, a significant proportion of patients were tested for HCV and the prevalence of HCV infection was high. Physicians appear to use a risk‐based screening strategy to identify HCV infection.

Successful integration of hepatitis C evaluation and treatment services with methadone maintenance.

Objectives:Despite high rates of hepatitis C virus (HCV) infection, relatively few current or former injection drug users receive evaluation and treatment for HCV. Here, we demonstrate the feasibility and effectiveness of integrating HCV care and methadone maintenance treatment (MMT). We hypothesized that colocation of these services would result in improved access to and utilization of HCV care. Methods:In this retrospective observational study, all patient charts from a single MMT clinic were reviewed 2 years after HCV care and MMT were integrated. Information obtained included screening for and counseling about HCV infection status, on-site HCV treatment and outcomes, and demographic and substance abuse data. Results:Two hundred ninety-one patient charts were reviewed. Two hundred eighty-one (99%) patients were screened for HCV antibody (HCV-Ab), and 188 (65%) were positive. Forty-nine (17%) patients were HIV/HCV coinfected. Ninety-eight percent of the HCV-Ab-positive patients received HCV counseling. Hundred fifty-nine (85%) of the HCV-Ab-positive patients were eligible to receive further evaluation and treatment for HCV on site, and 125 (78%) accepted. Hundred eighteen (94%) patients were tested for chronic HCV, and 83 were determined to have chronic HCV. Twenty-five patients received liver biopsy; low-stage disease was found in 7 patients. Twenty-one patients initiated HCV treatment. Sustained viral response was achieved in 8 patients. Seventeen patients had contraindications to HCV treatment. Further workup was prevented or delayed in 45 patients for various reasons, most commonly due to personal choice (29 patients). Conclusions:This study demonstrates that current and former injection drug users can be engaged successfully in evaluation and treatment of HCV infection when these services are collocated with MMT.